A portion of the disclosure of this patent document contains material that is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the Patent and Trademark office patent file or records, but otherwise reserves all copyright rights whatsoever.
The present invention relates generally to intraocular lenses used for the treatment of myopia.
More particularly, this invention pertains to methods of determining the power of a phakic intraocular lens based on the needs of a specific patient.
Refractive error is a mismatch between the power of the eye""s optical components (primarily the cornea and lens) and the axial length of the eye, such that when the eye is in its relaxed state the retinal image of a distant object will be blurred. Myopia (sometimes called nearsightedness) is a term used to describe faulty vision caused by an error of refraction in which rays of light entering the eye are brought into focus in front of the retina, usually as a result of the eyeball being too long from front to back. Eyeglasses and contact lenses are typically used to correct myopia.
The term phakic is applied to characterize an eye in which the natural ocular lens is still present. Conversely, an aphakic eye is one from which the natural ocular lens has been removed. A phakic eye is considered a dynamic or active eye because the living natural lens is subject to change over time, while an aphakic eye is considered a static eye because the natural lens has been removed.
Phakic intraocular lenses (xe2x80x9cIOLsxe2x80x9d) have been shown to be effective as a surgical correction for myopia. There appears to be no other suitable surgical alternative in cases of extremely high myopia or thin cornea. Phakic IOLs are now finding place in the surgical treatment for mid-range myopia and hyperopia as well. However, if the phakic IOL is to compete with LASIK (Laser Assisted in-Situ Keratomileusis) for mid range refractive error, careful attention must be paid to the refractive outcome. A LASIK patient slightly under or over corrected may undergo an enhancement procedure with little risk or loss of time. Lens exchange, on the other hand, probably involves more risk and presents a less suitable alternative. A precise power prediction for the IOL is, therefore, most important. Two theoretical phakic IOL formulas have been published. These formulas include characteristics that differ in important ways from aphakic IOL formulas.
Anterior chamber phakic IOLs were introduced by Strampelli and Barraquer in the 1950s. During the ensuing 15 years, over half of the 450 implanted lenses were explanted because of corneal endothelial damage or other complications. Phakic IOLs hold refractive advantages to LASIK for the treatment of high myopia especially when corneal thickness is a limiting factor. Despite early complications, the obvious clinical importance of this technique has spurred renewed interest.
Phakic IOLs include 3 basic designs: (1) posterior chamber lenses called ICLs (intraocular contact lenses) (sometimes referred to as Fyodorov or Staar Collamer lenses); (2) a variety of anterior chamber angle-supported lenses after the Kellman four point Multiflex IOL (Nuvita by Bausch and Lomb, Domilens or ZB5M by Chiron, and ZSAL-4 by Morcher GmbH); and (3) iris-stromal-supported lenses after Prof Jan Worst of the Netherlands (the Artisan lens from OPHTEC).
Fyorodov was the first to introduce the posterior chamber silicone ICL for the correction of myopia. He and his colleagues implanted over 1000 silicon posterior chamber intraocular lenses in phakic eyes. Brauweiler and his co-authors reported an 81.9% rate of secondary cataract formation at 2 years post-implantation.
Subsequent studies with the Staar Collamer posterior chamber ICL have indicated more favorable results. However, complications continue to include narrow angle glaucoma, retinal detachment, and cataract. Trindade utilized ultrasound biomicroscopic imaging to evaluate posterior chamber phakic ICLs. There was a consistent reduction in anterior chamber depth and localized narrowing of angle opening. Pesando and co-authors reported acute angle closure glaucoma to be 13.33% with the collamer posterior chamber phakic lens. Other problems including IOL-iris touch, IOL-crystalline lens touch, and anterior chamber shallowing raise concerns of pigmentary dispersion, cataractogenesis, as well as narrow angle glaucoma following posterior phakic intraocular lens implantation.
Modifications of the Kellman Multiflex, phakic angle supported lens have shown reduced rates of complications compared to phakic posterior chamber lenses. The Baikoff ZB lens was associated, however, with high endothelial cell loss. Subsequently, the ZB5M lens provided for 0.6 mm greater corneal clearance, and clinical studies have shown a reduced long-term endothelial cell loss. A fourth generation modification, the ZSAL-4 lens from Morcher GmbH has 19 degree haptic angulation to reduce iris contact and a 5 mm optic to reduce glare. Transient low grade iritis, pupil ovalization from iris entrapment by haptics, and lens rotation remain problems. The mean endothelial cell loss was 4.8% at 24 months. Aho and co-authors found a potential risk of nuclear cataract after phakic IOL implantation in patients over 40 years of age and in those with axial myopia greater than 30 mm. However, cataract development is known to be 4 times more frequent in those with high myopia than in the general population. Furthermore, in eyes with axial length greater than 29.0 mm, the incidence is significant at age 50 years.
Fechner introduced the iris-claw anterior chamber lens conceived by Professor Jan Worst of the Netherlands. The design of the lens is intended: (a) to avoid AC angle contact; (b) to limit likelihood of endothelial contact by low profile design; (c) to provide adequate clearance of the implant from the iris and crystalline lens; and (d) to provide stability by fixation to mid-stromal iris.
U.S. clinical investigation, phase 1 and 2 and interim phase 3, for the Artisan myopia lens indicated an initial complication rate of 39% on initial visit to 10% on visit four, to 0% on visit seven. The Artisan lens offers an option for the correction of high degrees of myopia.
Phakic intraocular lenses have proven optically effective. However, the post-operative need for an over-correction with contact lenses or spectacles is more common with phakic IOLs as compared to LASIK. For example, Zaldivar, using the Starr Collamer Posterior Chamber I Lens reported a mean post-operative spherical equivalent refraction of xe2x88x920.78 +/xe2x88x920.87 (range of +1.36 to xe2x88x923.50 diopters). The conclusion was that improvements in phakic IOL formulas are needed to improve the predictability of refractive outcome. Refractive results with the Artisan lens have been better. Trial findings at 6 months indicated manifest spherical equivalent to be within +/xe2x88x920.5 D of predicted, and 78% within +/xe2x88x921.00 D predicted.
Modern intraocular lens power formulas were derived from the optical considerations outlined by Gullstrand in 1909. Fyodorov developed an aphakic IOL power formula in 1967 that was revised and published in 1975. Binkhorst developed a theoretical formula and published a calculation manual in 1981. In the prior art, calculations of appropriate IOL power are based on pre-operative measurements of corneal power, axial length, and estimated post-operative pseudophakic anterior chamber depth (ACD). However, as noted above, these prior art formulas vary in predictive value, particularly at the extremes of axial length. Error is uncontrollably introduced in clinical measurement and the effect of axial length and corneal curvature measurement error has been studied and appreciated clinically. However, the post-operative anterior chamber depth estimation has not been subject to precise clinical estimation for a variety of reasons, and the prediction of ACD may account for 20-40% of the total refractive prediction error. Applanation ultrasound biometry has been the standard for the estimation of axial length and ACD. Recently, ACD estimation using dual-beam partial coherent interferometry has been reported.
A linear multiple-regression model was derived to predict the anterior chamber depth. PCI data when applied to the Holladay and SRK/T formulae, yielded a mean average error (MAE) of 0.44 diopter (D) compared to 0.56 D and 0.57 D respectively when US biometry ACD data was applied. Short eyes tend to have shallow ACDs and long eyes tend to have deep ACDs after surgery. To compensate for error, xe2x80x9cfudgexe2x80x9d factors were applied to theoretical formulas. Factors that have been introduced to improve the IOL power calculation include the A constant (SRK), the surgeon factor, and the anterior chamber depth (ACD) factor. Dealing with variances introduced from variable post-operative ACD has proven to be challenging. When the pre-operative ACD is analyzed by multiple regression in combination with corneal height and axial length, this variable has been shown in some applications to be predictive for both anterior and posterior chamber lenses. The inclusion of lens thickness in the algorithm did reach statistical significance in the prediction of ACD.
The continuous curvilinear capsulorhexis (CCC) technique of lens implantation has helped preserve a more natural position of the IOL and thus in the prediction of the post-operative ACD. Incremental improvements in IOL formulas, both theoretical and regression, have provided MAE approaching 0.5 D. However, an undesirable range of error is reported in various studies. In order to appreciate the limitations inherent in the prediction of resultant refractive error, one must understand the underlying sources of error in IOL calculations and their contributions to the final refractive error. Regardless of the accuracy of any predictive formula, the outcome still depends on measurement accuracy as well as the validity of IOL constants used in the calculation. The A-constant, surgeon factor, and ACD constant must be derived for each type of IOL. The use of inappropriate constants will introduce a systematic error in the refractive outcome. Regression analysis is commonly used to optimize existing formulas. In this manner, systematic errors can be corrected regardless of origin. The disadvantage of using actual post-operative refractive data in optimization of formulas or constants within formulas is the large sample size required to obtain statistical significance.
Aphakic IOL formulas include theoretical, empirical (usually derived from regression analysis), and combined formulas. The predictability of aphakic IOL formulas has improved incrementally over more than and has been evaluated in several publications.
The predictability of aphakic IOL formulas is limited primarily by the lack of pre-operative knowledge of the refractive effect that removal of the natural lens will have. This uncertainty is caused by the inability to measure the precise optical characteristics of the natural lens in the eye before surgery and to predict with certainty the optical certainty the optical changes that will occur upon lens removal, a feature not shared with phakic IOL formulas. Once a stable aphakic refraction is achieved, natural lens optics can be determined based on IOL power, thickness, shape characteristics and its precise location within the anterior segment of the eye. Surgically induced corneal shape changes must also be taken into account in this determination.
Despite surgical anatomical alterations, it is possible to predict aphakic IOL power with great accuracy. To this end, theoretical formulas include pre-operative average keratometry, axial length, anterior chamber depth, presumed location of the IOL within the anterior segment, and refractive indices of the cornea, aqueous and vitreous. Some formulas also introduce correction factors to adjust keratometry for assumed corneal index of refractive error. Error introduced by retinal thickness is also accounted for in some formulas. Finally, a surgeon factor can be added.
Holladay has provided a theoretical formula to predict refractive outcome for anterior chamber intraocular lenses that was applied to seven Baikoff anterior chamber lenses and three Momose anterior chamber intraocular lenses. The mean absolute prediction error was 0.42 D (standard deviation +/xe2x88x920.60) and 0.57 D (standard deviation +/xe2x88x920.64) respectively. Input data required by the Holladay formula include spectacle correction, vertex distance, and corneal curvature. In addition, an intraocular lens constant based on the location of the lens within the anterior chamber is required. The van der Heijde formula is similar, requiring manifest refraction adjusted for vertex distance, corneal curvature, and anterior chamber depth. As typically applied in the prior art, the van der Heijde model for predicting post-operative intraocular lens power (PIOL) is as follows:       PIOL    =                  n                              N            ⁢                          /                        ⁢                          (                              K                +                                  SE                  xe2x80x2                                            )                                -          d                    +                        n                                    n              ⁢                              /                            ⁢                              (                K                )                                      -            d                          ⁢                  xe2x80x83                ⁢        where                                          n          =                      xe2x80x83                    ⁢                      1.336            ⁢                          xe2x80x83                        ⁢            refractive            ⁢                          xe2x80x83                        ⁢            index                                                        K          =                      xe2x80x83                    ⁢                      Mean            ⁢                          xe2x80x83                        ⁢            central            ⁢                          xe2x80x83                        ⁢            K            ⁢                          xe2x80x83                        ⁢                          (              keratometry                                                                                SE            xe2x80x2                    =                      xe2x80x83                    ⁢                      SE            ⁢                          xe2x80x83                        ⁢                          (                              spherical                ⁢                                  xe2x80x83                                ⁢                equivalent                            )                        ⁢                          xe2x80x83                        ⁢            at            ⁢                          xe2x80x83                        ⁢            VD            ⁢                          xe2x80x83                        ⁢                          (                              Vertex                ⁢                                  xe2x80x83                                ⁢                distance                            )                                                                                xe2x80x83                    ⁢                      0.0            ⁢                          xe2x80x83                        ⁢            mm                                                        d          =                      xe2x80x83                    ⁢                                    ACD              ⁢                              xe2x80x83                            ⁢                              (                                  anterior                  ⁢                                      xe2x80x83                                    ⁢                  chamber                  ⁢                                      xe2x80x83                                    ⁢                  depth                                )                                      -                          0.8              ⁢                              xe2x80x83                            ⁢              mm              ⁢                              xe2x80x83                            ⁢                              (                Myopia                )                                                        
When the van der Heijde model is used to predict the IOL power for Ophtec Artisan lenses implanted in multiple phakic eyes, the actual and residual IOL power data are shown in FIG. 9. These results show a root mean square error (Rsq) of 0.96 with a standard deviation (RMSE) of 0.5955. These data suggest that provide a consistently accurate result for a large number of patients when implanting intraocular lenses having a common physical configuration, an improved lens power prediction model is needed.
What is needed, then, is a method and model for allowing physicians and lens manufacturers to accurately and consistently predict the lens power needed for an intraocular lens used for the treatment of myopia in a specific patient so that when the patient is fitted with a lens that is manufactured with the predicted power, optimum refractive correction of the myopia is achieved.
The present invention provides improved predictability of the post-operative refraction using an intraocular lens (IOL), such as the Ophtec Artisan IOL, for correction of myopia in a phakic eye. Both pre-operative clinical measurement and the formula application are important for lens power calculations. Statistical regression analysis is applied to measurable pre-operative factors associated with each individual patient to determine which factors are most significant in accurately predicting the needed power in the intraocular lens (xe2x80x9cPIOLxe2x80x9d), how those factors should be weighted, and whether there are any interactions between factors that are predictive of lens power. After the factors and their weighting are determined, the treating physician obtains the data corresponding to those factors and supplies this data to the lens manufacturer for calculation of the PIOL. Alternatively, the physician can calculate the PIOL directly.
Therefore, the present invention includes a method of designing an intraocular lens for surgical implantation in a phakic eye, wherein the physician or lens manufacturer uses a first prediction model to make a prediction of lens powers for a plurality of test lenses having a common lens configuration, using a set of pre-operative factors for each of a corresponding number of myopic test patient eyes. The set of pre-operative factors are selected from a group of patient specific factors that can include pre-operative spherical equivalent (cycloplegic and/or manifest), vertex distance, anterior chamber depth, pre-operative average keratometry, desired post-operative spherical equivalent, and vertex distance. The physician or manufacturer then selects test lenses that will provide the predicted lens powers needed to provide the predicted post-operative refraction in the corresponding test patient eyes and surgically implants the test lenses. After the test eyes have stabilized, the physician obtains post-operative measurements of the actual post-operative refraction achieved in each of the test patient eyes. A multiple regression analysis of the actual post-operative measurements is performed as compared to the corresponding set of pre-operative measurements to identify and quantify which of the pre-operative factors have a statistically significant effect on accuracy of the predicted post-operative refraction. Then, using the identification and quantification of statistical significance determined by the multiple regression analysis, the first prediction model is modified to create a second prediction model. The physician/manufacturer obtains from the patient the pre-operative measurements selected from the group of patient factors as identified and used in the second lens power prediction model. Using the second lens power prediction model and pre-operative measurements obtained from the patient, the lens power is selected for the intraocular lens to be implanted in the patient. In a further embodiment of the invention, results from implantation of an IOL in a first eye of the patient can be used to further modify and enhance the prediction model for purposes of selecting the IOL power for the lens to be implanted in the patient""s second eye.
In accordance with another aspect of the invention, a method of calculating a predicted lens power needed to provide a desired post-operative spherical equivalent to correct myopia in a phakic eye of a patient using an intraocular lens includes determining certain pre-operative characteristics of the eye, including cycloplegic and manifest spherical equivalent, vertex distance, anterior chamber depth, and keratometry, and then using each of the determined characteristics in a lens power prediction model to calculate the predicted lens power.